Abstract
Protein kinase C (PKC) is a mediator of transmembrane signal transduction, important in cell growth and differentiation. Cell activation by extracellular signals is associated with a translocation of PKC from the cytosol to the membrane. We measured and compared PKC activity in cytosol and membrane fractions of normal and neoplastic colorectal tissue. Total and membrane-associated PKC activity in normal colorectal tissue was greater in patients (N=16) with colorectal cancer compared to that from patients with a normal colonoscopy (N=16),P<0.01. A similar trend was noted in PKC activity of normal colorectal tissue from patients with adenomas compared to patients with a normal colonoscopy. PKC activity (total, membrane-associated, percent membrane) was not different in neoplastic colorectal tissue compared to that of adjacent normal tissue. However, there was a considerable range of PKC activity noted in all groups, which would limit the utility of PKC activity as a marker for colorectal neoplasia.
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References
Nishizuka Y: Studies and perspectives of protein kinase C. Science 233:305–312, 1986
Ashendel CL: The phorbol ester receptor: A phospholipid regulated protein kinase. Biochem Biophys Acta 822:219–242, 1985
Craven PA, DeRubertis FR: Role of activation of protein kinase C in the stimulation of colonic epithelial proliferation by unsaturated fatty acids. Gastroenterology 95:676–685, 1988
Craven PA, Pfanstiel J, DeRubertis FR: Role of activation of protein kinase C in the stimulation of colonic epithelial proliferation and reactive oxygen formation by bile acids. J Clin Invest 79:532–541, 1987
Fitzer CJ, O'Brian CA, Guillem JG, Weinstein IB: The regulation of protein kinase C by chenodeoxycholate, deoxycholate and several structurally related bile acids. Carcinogenesis 8:217–220, 1987
Baum CL, Wali RK, Sitrin MD, Bolt MJG, Brasitus TA: 1,2-Dimethylhydrazine-induced alterations in protein kinase C activity in the rat preneoplastic colon. Cancer Res 50:3915–3920, 1990
Muto T, Bussey HJR, Morson BC: The evolution of cancer of the colon and rectum. Cancer 36:2251–2270, 1975
Boland CR, Montgomery CK, Kim YS: Alterations in colonic mucin occurring with cellular differentiation and malignant transformation. Proc Natl Acad Sci USA 79:2051, 1982
Luk GD, Baylin SB: Ornithine decarboxylase as a biologic marker in familial colonic polyposis. N Engl J Med 311:80–83, 1984
Maskens AP, Deschner EE: Tritiated thymidine incorporation into epithelial cells of normal-appearing colorectal mucosa of cancer patients. J Natl Cancer Inst 58:1221–1224, 1977
McGarrity TJ, Peiffer LP, Bartholomew MJ, Pegg AE: Colonic polyamine content and ornithine decarboxylase activity as markers for adenomas. Cancer 66:1539–1543, 1990
Bradford MA: A rapid and sensitive technique for the quantification of microgram amounts of protein utilizing the principle of protein dye binding. Anal Biochem 72:248–254, 1976
Kraft AS, Anderson WB, Cooper HL, Sando JJ: Decrease in cytosolic calcium/phospholipid-dependent protein kinase activity following phorbol ester treatment of EL4 thymoma cells. J Biol Chem 22:13193–13196, 1982
Craven PA, DeRubertis FR: Alterations in protein kinase C in 1,2-dimethylhydrazine induced colonic carcinogenesis. Cancer Res 52:2216–2221, 1992
Kopp R, Noelka B, Sauter G, Schildberg FW, Paumgartner G, Pfeiffer A: Altered protein kinase C activity in biopsies of human colonic adenomas and carcinomas. Cancer Res 51:205–210, 1991
Hashimoto Y, Chida K, Huang M, Katayama M, Nishihira T, Kuroki T: Levels of protein kinase C activity in human gastrointestinal cancers. Biochem Biophys Res Commun 163:406–411, 1989
Guillem JG, O'Brian CA, Fitzer CJ, Forde KA, LoGerfo P, Treat M, Weinstein IB: Altered levels of protein kinase C and Ca+2-dependent protein kinases in human colon carcinoma. Cancer Res 47:2036–2039, 1987
Kusunoki M, Sakanoue Y, Hatada T, Yanagi H, Yamamura T, Utsunomiya J: Protein kinase C activity in human colonic adenoma and colorectal carcinoma. Cancer 69:24–30, 1992
Parker PJ, Kour G, Marais RM, Mitchell F, Pears C, Schaap D, Stabel S, Webster C: Protein kinase C—a family affair. Mol Cell Endocrinol 65:1–11, 1989
Coussens L, Parker PJ, Rhee L, Yang-Feng TL, Chen E, Waterfield MD, Francke U, Ulrich A: Multiple distinct forms of bovine and human protein kinase C suggest diversity in cellular signaling pathways. Science 233:859–866, 1986
Pelosin J-M, Keramidas M, Souvignet C, Chambaz EM: Differential inhibition of protein kinase C subtypes. Biochem Biophys Res Commun 169:1040–1048, 1990
Kubo K, Ohno S, Suzuki K: Primary structures of human protein kinase C βI and βII differ only in their C-terminal sequences. FEBS Lett. 223:138–142, 1987
Clark EA, Leach KL, Trojanowski JQ, Lee VM-Y: Characterization and differential distribution of the three major human protein kinase C isozymes (PKCαm, PKCβ, and PKCγ) of the central nervous system in normal and Alzheimer's disease brains. Lab Invest 64:35–44, 1991
Sekiguchi K, Tsukuda M, Ogita K, Kikkawa U, Nishizuka Y: Three distinct forms of rat brain protein kinase C: Differential response to unsaturated fatty acids. Biochem Biophys Res Commun 145:797–802, 1987
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Supported by grant R29 CA45468 (T.J.M.) from the National Institutes of Health.
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McGarrity, T.J., Peiffer, L.P. Protein kinase C activity as a potential marker for colorectal neoplasia. Digest Dis Sci 39, 458–463 (1994). https://doi.org/10.1007/BF02088328
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DOI: https://doi.org/10.1007/BF02088328